New a-nor-b-homo-steroids

ABSTRACT

R being -H, an acyl group or a hydrocarbon radical. These compounds have progestative, anti-inflammatory and/or glucocorticoid action.   R9 for -H, -OR   R6 for . . H, . . lower alkyl or . . OR R7 for . . H, . . lower alkyl or . . OR   WHEREIN X stands for hydrogen or methyl, R1 for H2 or O   R being -H, an acyl group or a hydrocarbon radical.   A-Nor-B-homo-steroids corresponding to the general formula

United States Patent [191 Jeger et al.

[ 51 Sept. 11, 1973 NEW A-NOR-B-HOMO-STEROIDS [75] inventors: Oskar Jeger; Kurt Schaffner, both of Zurich, Switzerland [73] Assignee: Ciba-Geigy Corporation, Ardsley,

[22] Filed: July 8, 1969 [21] Appl. No.: 840,025

Related US. Application Data [60] Division of Ser. No. 382,643, July 14, 1964, Pat. No.

3,504,603, which is a continuation-in-part of Ser. No. 226,524, Feb. 3, 1963, abandoned.

[30] Foreign Application Priority Data Mar. 23, 1962 Switzerland 3533/62 [56] References Cited UNITED STATES PATENTS 3,040,093 6/1962 Muller et al. 260/586 H 3,138,635 6/1964 Muller et al. 260/586 H 3,192,266 6/1965 Muller et a1. 260/586 H Primary ExaminerLeon Zitver Assistant ExaminerGerald A. Schwartz Att0rneyHarry Goldsmith, Joseph G. Kolodny and Mario A. Monaco [57] ABSTRACT A-Nor-B-homo-steroids corresponding to the general formula wherein X stands for hydrogen or methyl, R for H or O wm'uwflrm 20H Oacyl OH Oacyl R5101 =0, :Hg, or

R for H, lower alkyl or OR R for H, lower alkyl or OR 0 0-K OR R3 for =0, lower alkylene, or O H R being -H, an acyl group or a hydrocarbon radical.

These compounds have progestative, anti-inflammatory and/or glucocorticoid action.

8 Claims, No Drawings NEW A-NOR-B-I-IOMO-STEROIDS CROSS-REFERENCE TO RELATED APPLICATIONS This is a division of our application Ser. No. 382,643, filed July 14, 1964 (now US. Pat. No. 3,504,003), which itself is a continuation-impart of our application Ser. No. 226,524, filed Mar. 20, 1963 (now abandoned).

BACKGROUND OF THE INVENTION The present invention relates to the manufacture of A-nor-B-homosteroids, more particularly 3-oxoand 3:6-dioxo-A-nor-B-homosteroids, starting from 3-oxo- 4:5-oxidosteroids, and to new compounds of this class which are biologically active or represent intermediates for the manufacture of biologically active compounds. Such are e.g. the 3:6-dioxo-A-nor-B-homo-androstanes and -A-androstenes, which have in position 175 a free or esterified hydroxyl group, and also the corresponding 3-mono-oxo-compounds; they display a high anabolic activity coupled with a very low androgenic activity. The 3:6-dioxo-A-nor-B-homopregnane compounds, more especially those which contain in position 20, and possibly in position ll, an oxo group, in positions 17 and/or 21 and 1 1/3 hydroxyl groups, are of very special importance as novel compounds having a progestative or anti-inflammatory action respectively. Other compounds, such as the A-nor-B-homo-steroids of the androstane and pregnane series, which have substituents which might be converted into those named above typical for the biologically active compounds, are important as intermediates for said active compounds. This also applies to the other steroid series such as the A- nor-B-homo-steroids of the cholane, cholestane, spirostane, cardanolide, and bufanolide series. They may be transformed in a manner known per se into the active compounds of the androstane and pregnane series, for example, by an acylolytic, oxidative or microbiological method.

The hitherto known steroids having the A-nor-B-' 6-oxo-A-nor-B- and homo skeleton namely homocholestane and 6-oxo-l7B-hydroxy-5a- -SB-A-nor-B-homo-androstane and their l7-benzoates The 3-oxo-4a:5aand 4B:5fi-oxidosteroids, saturated in positions I and 2, used as starting materials can be prepared in the manner known per se from the corresponding A-3-oxo compounds, for example by treatment with alkaline hydrogen peroxide or per-acids, or by hydrogenation of A -3-oxo-4:5-oxidosteroids. The last-mentioned starting materials are new; surprisingly, they can be obtained directly from A'-3-oxosteroiddienes by treatment with per-acids, for example with organic per-acids, such as lower aliphatic or aromatic per-acids, for example with peracetic, perbenzoic and monoperphthalic acid, or by dehydrogenation of the above-mentioned 1:2-satu rated 3 -oxo-4 5 oxidosteroids, for example with selenium dioxide or dicyano-dichloroquinone.

The irradiation according to the invention o f 3-oxo- 4:5-oxidosteroids is advantageously performed in an organic solvent, for example in an aliphatic or cycloaliphatic hydrocarbon such as pentane, hexane or methylcyclohexane. Particularly suitable are aliphatic and cyclic ethers such, for instance, as diethyl ether or dioxane.

Suitable light is artificial or strong natural light; it is advantageous to use ultra-violet light such as is emitted by mercury low-pressure or high-pressure burners, or strong sunlight. The irradiation is advantageously performed at a temperature ranging from 0 to +C.

In "the'3 dioxo A-nor-fi-homosteroids obtained as reaction products, which, being B-diketo compounds are predominantly present in the enol form, any present ester or protective groups such, for example, as ketals or bismethylenedioxy groups, may be split hydrolytically and free hydroxyl groups may be oxidized to oxo groups. On the other hand, the products of the present process may be converted in the known manner into their functional ketone derivatives derived from the enol form, or into metal salts. Thus, for example, acylation (for example treatment with a carboxylic anhydride, such as acetic or propionic anhydride) yields the corresponding enol esters; with etherifying agents such, for example, as alcohols or thioalcohols in the presence of an acid catalyst, the enolethers and, respectively, thioenolethers are obtained. When the products of the present process are reacted, for example with hydrazines, cyclic hydrazones are obtained which may also be looked upon as pyrazole derivatives. Reaction with cupric salts furnishes the corresponding copper complexes.

The 5 -3-oxo-6-acyloxy-A-nor-B-homosteroids prepared by the present process can be converted into the corresponding saturated -unsubstituted 3-oxo-A-nor- B-homosteroids by catalytic hydrogenation in a manner known per se, such as hydrogenation, for example, in benzene or alcohol, with palladium carbon or palladium-barium carbonate catalyst.

The 3-oxo-4a:5aand 4B5B-oxidosteroids used as starting materials in the present process belong preferably to the androstane, pregnane, cholane, cholestane, spirostane or cardanolide series or to the corresponding l9-nor series and may contain, in addition to the aforementioned groupings, in one or more than one of the positions 1, 6, 7, 8, 9, l1, 12, 14, 15 2i further substituents such as alkyl (for example methyl) groups and/or halogen atoms, free or functionally converted oxo groups, or free, esterified or etherified hydroxyl groups. Furthermore, the starting materials may coni i TR. 8:

tain double bonds, more especially as mentioned above, between carbon atoms 1 and 2. It is also possible to use a mixture of the two 4:5-isomeric epoxides.

- Particularly important starting materials are, for example, the following compounds: 5 3-oxo-4a5a-oxidoand -4B:5B-oxido-l7- hydroxyandrostane and its esters, 3:l7-dioxo-4a:5a-oxidoand -4B:5/3-oxidoandrostane and its l7-ethyleneketal,

hydroxypregnane and their esters, 3:20-dioxo-4m5a-oxidoand -4fi:5B-oxido-l7a:21- dihydroxy-pregnane, their esters and l7:20;20:2l-bis-' methylenedioxy compounds, 3:20-dioxo-4az5a-oxidoand -4B:5B-oxidol1B:l7az2l-tri-hydroxypregnane, their esters and 172- 20;20:2l-bis-methylenedioxy compounds, inter alia, for example, the lactone of A -3-oxo-4z5-oxido-l7fihydroxy-l7a-(B-carboxyethyl)-androstene and the ldehydro-4:5 oxidotestolo'lactone; furthermore the derivatives, unsaturated in positions 1 and 2, of the above compounds. The 17-oxo or 20-oxo compounds are advantageously used in the form of their 17- monoketals or 20-monoketals.

Another object of the invention are the 3:6-dioxo-A- nor-B-homosteroids, obtained by the present process, and their functional derivatives such, for example, as their enolesters (derived from the tautomeric enol a form) of organic, more especially lower aliphatic or aromatic carboxylic or sulfonic acids, such, for example, as acetic, propionic, butyric, benzoic, para-toluenesulfonic acid, and enolethers and enolthioethers, for example lower alkyl ethers and thioethers (such as methyl-, ethyland propyl-ether and thioether) as well as the corresponding metal salts, for example copper complexes.

Especially valuable compounds are such of the formulae l and ll I i R5 ...R

and

OR 03' OR OR r 1 and H lower alkyl lower alkenyl loweralkinyl R for a member selected from the group consisting of OH OH Oacyl 1.( .g

H H H and R and R for a member selected from the group consisting of. H, lower alkyl and O R, R together with R a member selected from the group consisting of for a member selected from the group consisting of =0,

R for a member selected from the group consisting of -H and -O-R and R is a member selected from the group consisting of -H, an acyl group, a hydrocarbon radical, X and Y each is a member selected from the group consisting of hydrogen and methyl, and the ldehydro derivatives, tautomeric forms and the enol esters and ethers thereof, with the proviso that R in 1,2-

saturated compounds be different from when X is hydrogen, that R be different from acyl in R and R when taken together and that the ether groups are derived from alcohols having from one to 8 carbon atoms and the esters are derived from acids having from one to 15 carbon atoms.

The compounds of formula I in which R, stands for a free' or esterified or etherified hydroxyl group together with a hydrogen atom or a lower alkyl group exhibit a high anabolic action. When there is a lower alkyl group in l7a-position together with the l7B-hydroxyl group, the anabolic action develops also upon peroral administration. These compounds are therefore suitable for use as medicaments for the treatment of all conditions requiring an increased protein synthesis, such as chronic loss in weight, post-operative and postinfection conditions, anorexia and osteoporosis, more especially in geriatry. Particularly suitable are the following compounds: 3z6-dioxo-l7B-hydroxy-A-nor-B-homo-androstane and its esters,

3 :6-dioxo-l 7B-hydroxy-l 7oz-alkyl-A-nor-B-homoandrostanes and their esters,

3 :6-dioxo- 1 7B-hydroxy-l 7a-alkyl-A-nor-B-homooestranes and their esters,

and 7aa-lower alkyl derivatives of these compounds and the l-dehydro-derivatives of all these compounds. As specific compounds there may be mentioned for instance:

the 3:6-dioxo-l7B-hydroxy-A-nor-B-homoandrostane the 3:6-dioxo-l 7B-acetoxy-A-nor-B-homo-androstane the 3 :6-dioxol 7B-isobutyryloxy-A-nor-B-homoandrostane the 3:6-dioxol 7B-valerianyloxy-A-nor-B-homoandrostane the 3 :6-dioxo-1 7B-undec'enyloxy-A-nor-B-homoandrostane the 3 :6-dioxo-l 7B-decanoyloxy-A-nor-B-androstane the 3:6-dioxo- 1 7B-( phenylpropionyloxy)A-nor-B- homo-androstane the A'-3 :6-dioxol 7fl-acetoxyl -methyl-A-nor-B- homo-androstene the A -3z6-dioxol7fi-acetoxy-A-nor-B-homo-oestrene the 3:6-dioxo-l7B-hydroxy-7aa, l7a-dimethyl-A-nor- B-homo-androstane. Outstanding anabolic properties have the compounds: 3:6-dioxol 7fl-hydroxy-l 7a-methyl-A-nor-B-homoandrostane 3 :6-dioxol 7B-hydroxyl 7a-methyl-A-nor-B-homooestrane and the 3 :6-dioxol 7B-hydroxy-7aa, l7a-dimethyl-A-nor-B- homooestrane and their l-dehydro-derivatives.

The anabolic effect may be measured pharmacologically in fully grown, male castrated rats by the socalled levator-ani test, by giving the animals increasing doses of the substance to be tested and measuring the increasing weight of the involuted levator ani muscle. An optimal effect may be considered that which represents a full restitution of the muscle to the weight of that muscle in normal control animals. Such complete restitution is attained with very small doses of the substances of the present invention. For instance, when 3 :6-dioxol 7B-hydroxyl 7a-methyl-A-nor-B-homoandrostane is administered subcutaneously, the optimal anabolic effect corresponding to said complete restitution is attained with a dose of approximately 0,3 mg/kg daily, for days. The androgenic effect of the substance may similarly be measured by determining the increase in weight of the involuted seminal vesicles of the castrated animals. To compare the androgenic activity of the same substance with its anabolic effect the optimal androgenic dose, viz. that provoking a complete weight restitution of the seminal vesicles, as compared to the controls, is evaluated. In the above case of the 3 :6-dio xo-l 7B-hydroxy-l 7amethyl-A-nor-B-homoandrostane this androgenic dose is 13 to times higher than the optimal anabolic dose when the administration is effected by the subcutaneous route. This means that a very good dissociation between anabolic and an drogenic effect is present which is a prerequisite for an ideal anabolic treatment. In the other compound mentioned above, the 3:6-dioxo-l7fi-hydroxy-7aa, 17adimethyl-A-nor-B-homo-oestrane, these conditions are still more favorable, the ratio between the doseeliciting the optimal androgenic effect and the dose eliciting the optimal anabolic effect being about 100, when the substance is administered subcutaneously and about 30 70 on peroral administration. The absolute value of the anabolic effect is extremely high with this compound, the optimal dose under the afore-mentioned experimental conditions being 0'.03 mg/kg body weight daily for 15 days when given subcutaneously and 1.0 mg/kg daily for 15 days when given orally.

Compounds of the above formula I wherein R, stands for a free or esterified or etherified hydroxyl group together with an unsaturated hydrocarbon radical, especially a vinyl, allyl, ethinyl or propinyl group, which may also be halogenated, e.g., fluorinated, show a gestagenic or ovulation inhibiting action. Especially active are the oestrane compounds and their l-dehydro derivatives, for example A -3 :6-dioxol 7,6-hydroxyl 7a-vinyland 1 7aethinyl-A-nor-B-homo-androstene and their esters and A -3:6-dioxo-l7B-hydroxy-l 7a-vinyland -l 7aethinyl-A-nor-B-homo-oestrene and their esters.

Compounds of formula II above in which R, stands for an oxo group and R for a hydrogen atom, exhibit a pronounced progestative action. Special mention deserve 3:6:20-trioxo-A-nor-B-homo-pregnane,

3 z6z20-trioxol 7a-hydroxy-A-nor-B-homo-pregnane and its esters,

A'-3z6:20-trioxo-A-nor-B-homo-pregnene A-3 26:20-trioxol 7a-hyd roxy-A-nor-B-homopregnene and its esters, 3:6:20-trioxo l6, l7 dihydroxy-A-nor-"B-homopregnane, and their 6-enol-esters and/or l7 esters or ethers, for example the 6- or l7a-acetates or 16a, 17aacetonides of the 1601, l7a-dihydroxy derivatives.

Compounds of the above formula II wherein R is a free, an esterified or etherified hydroxyl and R is an oxo group are distinguished by their antidnflammatory and glucocorticoid action and may thus be used in the treatment of inflammatory diseases of the joints and their surroundings, for example polyarthritis, in acute and chronic rheumatic fever and in the form of creams and salves in dermatology for the treatment of eczema of diverse origin. Especially active are in this respect compounds of the formula CHa OHi o i i oo-om-n:

' CH: O o

wherein R represents a hydrogen atom or a methyl group and R is a free or esterified hydroxyl group as well as 6-enol-esters or 6-enol-ethers thereof. As specific compounds'there may be mentioned particularly the A'-3:6:l 1:20-tetraoxol 701:2 l -dihydroxy-A-nor-B- homo-pregnene, its lower aliphatic carboxylic acid es ters, such as the acetate, the trimethylacetate, the propionate, valerate caproate etc., and the 7-methylderivatives of these compounds.

All compounds of formulae 1 and [1 above may also be employed in veterinary medicine, e.g., as additives to animal fodder.

The acyl radicals in the above-mentioned esters are more especially those of aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic carboxylic acids containing one to 15 carbon atoms, for example formiates, acetates, propionates, butyrates, trimethylacetates, caproates, valerates, oenanthates, decanoates, undecylenates, cyclopentylpropionates, hexahydrobenzoates,

phenylpropionates, benzoates, furoates, trifluoracetates, ethyl or methyl carbonates, or the like.

Ethers are primarily derived from aliphatic, araliphat'ic, cycloaliphatic or heterocyclic alcohols preferably having from 1 to 8 carbon atoms, for example from methanol, ethanol, propanol, benzyl alcohol, cyclopentanol or tetrahydropyranol, e.g., the radical therefrom may be methyl, ethyl, propyl, benzyl, cyclopentyl or tetrahydropyranyl.

In the case of 3,6-dioxo-17B-hydroxy-A-nor-B- homo-androstane or '-oestrane compounds or their 1- dehydro-derivatives, 6-mono-esters and. 6-monoethers, as derived from the enol form of the steroids said, as well as 17-mono-est ers or ethers or 6, 17- diesters or diethers may be prepared from the unesterified compounds. Thus, for example, by acylation of a 3 ,6-dioxo-17a-a1kyl-17B-hydroxy-androstane or oestrane compound, for example, by treatment with carboxylic acid anhydride such as acetic or propionic anhydride at room temperature, the 6-enolesters are obtained, whereas treatment with an etherifying agent, for

example an alcohol, such as an alkanol, in the presence of an acidic catalyst gives rise to the corresponding enolethers. To obtain 6, '17-diesters the acylation is preferably performed at elevated temperature. In the 6, 17-diesters thus obtained it is possible to liberate the 6-enol ester group by acid hydrolysis, thus rendering accessible the 17-monoesters. When there is no hydrocarbon in 17a-position, the acylation affords preferably the 6, 17a-diesters, from which there are obtained 6- mono-esters by mild alkaline hydrolysis and 17-monoesters by acidic hydrolysis.

From 2 l-hydroxy-20 keto-A-nor-B-homo-pregnane derivatives or their l-dehyrdo-derivatives, such as for instance the above named A'-3,6,11,20-tetraoxo- 17a,21.-dihydroxy A-nor-B-homo-pregnene, there are obtained, under mild condition, 21-esters, and, then, after longer periods of acylation, the 6,21-diesters. In the latter it is possible to saponify'only the 6-ester group by acid hydrolysis, or only the 21-ester group by mild alkaline hydrolysis. There can thus be prepared 6- and 21-mono-esters as well as 6,21-diesters.

The new pharmacologically active compounds can be used for the manufacture of pharmaceutical preparations. These contain said active compounds together with a solid or liquid medicinal excipient. More particularly the preparations of the present invention are characterized by the content of one of the new A-nor- B-homo-steroids. The preparations are made by as such known methods, for example, with the use of pharmaceutical organic or inorganic excipients, suitable for parenteral, enteral' and particularly oral, or'also topic administration. Suitable excipients are substances that do not react with the new compounds such, as for example, water, vegetable oils, benzyl alcohols, polyethylene glycols, gelatine, lactose, starch, magnesium stearate, talc, white petroleum jelly, cholesterol or other medicinal excipients. More especially, preparations are made which are suitable for parenteral administration, preferably solutions, above all oily or aqueous solutions: furthermore suspensions, emulsions or implants;

for enteral administration there are also made tablets or dragees, and for local administration also ointments or creams. If desired the preparations may be sterilized or they may contain assistantssuch as preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure or buffers. They may also contain 8 other therapeutically active compounds. They are prepared in the known manner. The content of the active substance in these preparations, such as of a tablet, is preferably 0.01-20 mg or 0.03 50%, especially 0.1 to 10 by weight. Said pharmaceutical preparations can be used in human or veterinary medicine.

The process is described more fully in the following Examples. The ultra-violet absorption spectra have been established in ethanolic solutions and the specific rotations were measured in a chloroform solution in a tube of 10 cm length.

The irradiation with ultra-violet rays is performed under nitrogen in a quartz vessel in which the source of light is centrally disposed and which'is cooled by means ,of water. The light sources used are low-pressure burn- EXAMPLE 1 A mixture of 15 grams of l-dehydrotestosterone acetate and a solution of perbenzoic acid in ml of chloroform (8.5 mg per ml) is kept for 4 days in the dark at room temperature. The reaction solution is then diluted with ether and agitated successively with aqueous solutions of potassium iodide and sodium thiosulfate. A partially crystalline crude product is obtained which is chromatographed on alumina. A 2:1-mixture of benzene and hexane elutes 3.6 grams of a crystalline fraction, while a 1:1-mixture of benzene and 'ether elutes 7.5 grams of unchanged startingmaterial.

The first fraction is recrystallized four times from acetone+hexane and furnishes 2.15 grams of A -3-ox0- 4B:5B-oxido-17B-acetoxyandrostene. Constant melting point: 144 C. Optical rotation [(110 +250 (c 1.02). Ultra-violet spectrum: A 232 p. (log or 3.96). Infra-red spectrum (in chloroform): 11 1,725, 1,680, 1,623, 1255 cm.

After 2 recrystallizations from acetone+hexane and 8 from ethanol the mother liquor products furnish 130 mgof A-3-oxo-4a:5a-oxido-17B-acetoxyandrostene having a constant melting pointof 139 141C. Ultraviolet spectrumzlt 227.5 p, (log e= 4.02). Infra-red spectrum (in chloroform): u= 1722, 1677, 1612, 1256 cm.

EXAMPLE 2 200 mg of A-3-oxo-4B:5B-oxido-17B- acetoxyandrostene are hydrogenated in the presence of 200 mg of palladium black of 5% strength in-lOml of benzene. When the absorption of hydrogen (1 mol) ceases, the solution is filtered through Celit, evaporated under vacuum, and the residue is recrystallized from acetone+hexane. Melting point: 153 155C. Ultra-violet spectrum final absorption at 210 a (log 6 3.36). Infra-red spectrum (in chloroform): v 1,725, 1,260 cm'f. Optical rotation [01] +131 (c 1.85). As revealed by the mixed melting point and the infrared spectrum the product is identical with authentic 3- oxo-4Bz5B-oxidol 7B-acetoxyandrostane; melting point 153 155C; optical rotation [01],, +135 (c 1.30).

EXAMPLE 3 30 mg of A -3-oxo-4a:5a-oxido-l7B- acetoxyandrostene are hydrogenated with 30 mg of palladium black of 5% strength in 3.5 ml of benzene as described in Example 2 for A -3-oxo-4B:5B-oxido-17B- acetoxyandrostene. After crystallization from aceto ne+hexane the resulting product has a constant melting point at 164 165C. Optical rotation [11] -68 0.64). Ultra-violet spectrum: final absorption at 210 1. (log e= 3.49). infra-red spectrum (in chloroform) v=l7.l5, 1268 cm".

EXAMPLE 4 A solution of 2.0 grams of A-3-oxo-4B:5fl-oxido- 17B-acetoxyandrostene in 200 ml of dioxane is irradi ated for 40 hours with a low-pressure burner, and then evaporated under vacuum. In the thin-layer chromatogram [eluantz benzene+methanol 19:1] of the crystalline residue no starting material can be detected. After three recrystallizations from methylene chloride+methanol there are obtained 1.60 grams of A-3:6-dioxo- 17B-acetoxy-A-nor-B-homoandrostene (constant melting point+ 171 172C). Ferric chloride test: positive. Optical rotation [01] +98 0.65). Ultra-violet spectrum: A 239 p. (log 6 3.96), 3.11 p. (log 6 3.87). Infra-red spectrum: in chloroform: 11 1,730, 1,670, 1,618, 1,260 cm in Nujol: v 1,730, 1,658, 1,609, 1,567 (weak), 1256 cm.

EXAMPLE 5 A solution of 380 mg of A-3-oxo-4a:5a-oxido-l7B- acetoxyandrostene in 100 ml of dioxane is irradiated for 2 hours with a low-pressure burner and then evaporated under vacuum. In the thin-layer chromatogram [eluantz benzene+methanol 19 1] of the residue no starting material can be detected. By chromatography on silica gel with a 19:1-mixture of benzene and ether there are obtained 200 mg of crystals which, after-three recrystallizations from methylene chloride+methanol, melt at 164 166C (130 mg). Sublimation in a high vacuum at 150C yields pure A-3:6-dioxo-l7B- acetoxy-A-nor-B-homoandrostene melting at 171 172C which, according to its mixed melting point, specific rotation [01],, ==+93 (c 0.74) and infra-red spectrum, is identical with the photo product described above in Example 4.

EXAMPLE 6 450 mg of A'-3:6-dioxo-17B-acetoxy-A-nor B- homoandrostene are hydrogenated in the presence of 450 mg of palladium black of 5% strength in 50 ml of benzene. When the absorption of hydrogen has ceased (1 mol, after 30 minutes) the solution is filtered through Celit and the filtrate is evaporated under vacuum. The residue is chromatographed on silica gel. A 9:1-mixture of benzene and ether elutes 360 mg of crystals which, after three recrystallizations from methylene chloride+methanol, yield 310 mg of 3:6-dioxo- 17fi-acetoxy-A-nor-B-homoandrostane having a constant melting point of 154 156C. Ferric chloride test: positive. Optical rotation [01],, +47 (c 0.42). Ultraviolet spectrum: M, 291 1. (log e 3.96). Infra-red spectrum in chloroform: v= 1,721, 1,641, 1,608, 1,255 cm.

EXAMPLE 7 1.20 grams of 3-oxo-4B:5fl-oxido-l7B-acetoxyandrostane in 120 ml of dioxane are irradiated for 54 hours with a low-pressure burner, and the solution is then evaporatedunder vacuum. According to its thinlayer chromatogram leluant: 19:1-mixture of benzene and methanol] the residue contains starting material and about 25% of 3:6-dioxo-l7B-acetoxy-A-nor-B- homoandrostane. Ferric chloride test: positive. Ultraviolet spectrum: )t 293 p. (log e 3.32). The two compounds are very difficult to separate by chromatography on silica gel. Benzene elutes only 35 mg of uniform crystals which, after recrystallization from methylene chloride+methanol, melt at 154 156C. According to their mixed melting point, infra-red spectrum, ultra-violet spectrum (A 291 n; log e= 4.01) and specific rotation ([01],, =+44; c 0.64) they are identical with the photo product described in Example 6.

EXAMPLE 8 crystals which, after three recrystallizations from methylene chlofifie-l rnethanol, melt at 154-156C (100 mg) and according to their mixed melting point and infrared spectrum are identical with the compound described in Example 6.

EXAMPLE 9 mg of 3-oxo-4az5a-oxido-17B acetoxyandrostane in dioxane are irradiated in an open quartz reaction vessel for 10 hours with a low-pressure burner, and the solution is then evaporated under vacuum. According to the ferric chloride test (positive), thin-layer chromatogram (eluant: benzene+methanol 19:1] and ultraviolet spectrum (A 293 pt, log e 3.41) the residue contains, inter alia, starting material as well as about 28% of the photo product described in Example 6. The mixture is difficult to separate; it is chromatographed on silica gel, with benzene eluting about 4 mg of uniform crystals melting at 154 156C. According to its mixed melting point, infra-red spectrum and ultraviolet spectrum (A 291 t, log 6 3.97), the compound is identical with 3:6-dioxo-l7B-acetoxy-A-nor- B-homoandrostane.

EXAMPLE 10 440 mg of A-3:6-dioxo-17B-acetoxy-A-nor-B- homoandrostene are kept for 6 days at room temperature in 10ml of a 1:1-mixture of acetic anhydride and pyridine. The solution is then evaporated to dryness under vacuum and the crystalline residue is dissolved in 9:1 benzene+ ether and filtered through silica gel, to yield 350 mg of A -3-oxo-6:17B-diacetoxy-A-nor-B- homoandrostadiene which, after three recrystallizations from acetone+hexane, melts at 120 121C. Ferric chloride test: negative. Optical rotation [01],, +103 (c 0.91 Ultra-violet spectrumm 248 (loge=3.94). Infra-red spectrum in chloroform: 1,755, 1,722, 1,703, 1,649, 1,595, 1,255, 1,165 cm.

EXAMPLE 11 200 mg of A-3 :6-dioxo- 17fi-acetoxy-A-noFEhBihdfiifiEfi'h' are hydrolyzed for 24 hours at room temperature in 5 ml of saturated methanolic potassium carbonate solution. Extraction with ether furnishes 150 mg of A-3:6- dioxo-l73-hydroxy-A-nor-B-homoandrostene which, after three recrystallizations from methanol, displays a constant melting point at 156 l59C. Infra-red spectrum (in Nujol): v= 3,560, 1,671, 1,614 cm. Optical rotation [(11 +107 (0 1.0). Ultra-violet spectrumzlt 240 u, 311 p. (log 3.91, 3.82).

EXAMPLE 1;

A solution of 80 mg of A-3:6-dioxo-17B-acetoxy-A- nor-B-homoandrostene in '20 ml of ethanol is mixed with a solution of 0.5 gram of copper acetate and 2 grams of sodium acetate in 20 m1 of water, whereupon the reaction solution turns instantaneously green. After minutes it is poured into water and extracted with benzene. Evaporation of the organic phase under vacuum yields 94 mg of green crystals which, according to their thin-layer chromatogram [eluant: benzene:methanol 19:1], are uniform. After three recrystallizations from methylene chloride+ methanol there are obtained 40 mg of the copper complex of A -3z6-dioxo-l7flacetoxy-A-nor-B-homoandrostene which decomposes at 300 310C. Ultra-violet spectrum: A 332 1. (log e 4.14), 246 p. (log 6 4.31 Infra-red spectrum in chloroform: v= 1721, 1595, 1565, 1498,1260cm.

EXAMPLE 13 EXAMPLE 14 A solution of 80 mg of 3:6-dioxo-l 7B-acetoxy-A-nor- B-homoandrostane in ml of ethanol is mixed with a solution of 0.5 gram of copper acetate and 2 grams of sodium acetate in 20 ml 'of water. The solution immediately turns green and after '15 minutes it is poured into water, and with benzene 90 mg of green crystals are isolated which, according to their thin-layer chromatogram [eluant benzene+methanol 19:1], are uniform. After having been recrystallized five times from methylene chloride+methanol the resulting copper complex of 3:6-dioxo-l7B-acetoxy-A-nor-B-homoandrostane decomposes at 300 310C. Ultra-violet spectrumzlt 310 n (log a 4.33), 259 1. (log it 3.95). Infra-red spectrum in chloroform: v= 1,720, 1,578, 1,475, 1,260 cm.

' EXAMPLE 15 A mixture of 300 mg of 3:6-dioxo-17B-hydroxy-A- nor-B-homoandrostane, 2ml of hydrazine hydrate and 10 ml of ethanol is heated in a bomb tube for 16 hours at 210C. The cooled solution is then evaporated to dryness under vacuum and the resulting crystals (300 mg) which according to their, thin-layer chromatogram [eluant: benzene+ methanol 10:1]are uniform are recrystallized twice from methanol, to yield the pyrazole derivative of 3:6-diox0-17fl-hydroxy-A-nor-B- homoandrostane which has a constant melting point at 152 155C. Optical rotation [01],, +57 (c 0.52). Infra-red spectrum in chloroform: v 3,630, 3,640, 1,635 cm (weak). Ultra-violet spectrumx 227 p.(log e 3.74).

EXAMPLE 16 3 grams of 3-oxo-4Bz5B-oxido 1 7B- acetoxyandrostane and 900 mg of selenium dioxide are mixed with 150 ml of tertiary butanol and 1.5 ml of glacial acetic acid. The suspension is reflexed for 24 hours under nitrogen, then another 900 mg of selenium dioxide are added and the whole is boiled for 24 hours longer. The cooled solution is freed by decantation from the precipitated selenium, evaporated and the residue is dissolved in ethyl acetate. The organic solution is washed successively with dilute potassium bicarbonate solution, water, a freshly prepared ice-cold ammonium sulfide solution, ice-cold dilute ammonia solution, and .water. After several recrystallizations from acetone+hexane there are obtained 2 grams of A'-3- oxo-4B:5B-oxido-l7B-acetoxyandrostene melting at A In an analogous manner 4i3:5fl-epoxy-l9-nortestosterone acetate yields l-dehydro-4/3:5B-epoxy-l 9-nortestosterone acetate.

EXAMPLE 17 9 grams of A -3-oxo-l7a-methyl-l7B-hydroxyandrostadiene in a solution of perbenzoic acid in 140 ml of chloroform (35 mg per ml) are kept for 4 days in the dark at room temperature. The reaction solution is then diluted with ether and agitated with aqueous potassium iodide solution and then with aqueous sodium thiosulfate solution, to yield 9.1 grams of a crude product which is chromatographed on neutral alumina (activity Ill; 30 times the amount).

Benzene and a 9:1-mixture of benzene+ether elute 1,830 mg of amorphous material which is once more chromatographed on neutral alumina (activity 111; 60 times the amount). A 9: l-mixture of benzene and ether elutes 1,015 mg of crystalline material which, after two recrystallizations from acetone-l-petroleum ether, melts at 167C (800 mg). Optical rotation [01],, l05.l (c 0.56). Ultra-violet spectrumzlt 232 p. (e 9,000). lnfra-red spectrum: u 3,600, 1,674, 1,617 cm".

The product is a mixture of 85% of 3-oxo-4flz5floxido-l7fl-hydroxy-17a-methyl-A -androstene and 15% of 3oxo-4a:5cz-oxido-'17B-hydroxy-l7a-methyl- A -androstene. The ether fractions from the two chromatograms, after one crystallization from acetone+petroleum ether, yield 5.3 grams of unchanged starting material.

700 mg of the above mixture are irradiated in 200 ml of dioxane for 46 hours. The solution is then evaporated under vacuum. After having twice reprecipitated the crystalline crude product there are obtained 458 mg of A'3z6-dioxo-l7a-methyl-17B-hydroxy'A-nor-B- homoandrostene melting at 126 128C. Optical rotation [01],, =+79.8(c 0.49). Ultra-violet spectrumzk 239 p.(e 8,200) and 311 p. (e 6,700). Infra-red spectrum v 3,610, 1,761, 1,708 cm.

EXAMPLE 18 Under the conditions described in Example 4 the bismethylenedioxy compound of prednisolone yields via the corresponding 4az5a-oxido or 413:5]S-oxido compound (prepared as described in Example 1) the 17 :20- ;20:2l-bis-methylenedioxy compound of A-3:6:20- trioxo-l 16:1701:2l-trihydroxy-A-nor-Bhomopregnene which, on hydrolysis, furnishes free A-3:6:20 trioxol 1B:1701:2l-trihydroxy-A-nor-B-homopregnene.

An analogous irradiation treatment of the A'-3-oxo- 4a:5aand -4B:5fl-oxido-17/3-acetoxy-l9- norandrostene described in Example 16 yields A-3:6- dioxol 7B-acetoxy-A-nor-B-homol 9-norandrostene.

EXAMPLE 19 A solution of 200 mg of 3:6-dioxo-17B-acetoxy-A- nor-B-homandrostane in 10 ml of glacial acetic acid saturated with hydrochloric acid is mixed with 2 ml of methylmercaptan. After 48 hours the reaction mixture is worked up, to give a substantially quantitative yield of A -methylmercapto-6-oxo-17B-acetoxy-A-nor-B- homo-androstene melting at 166 167C. Optical rotation [01],, +124(c 0.67). Ultra-violet spectrum:)t,,,,, 319 p. (log e= 4.02). Infra-red spectrum in chloroform: v= 1720, 1624, 1255 cm". On reductive desulfurization with Raney nickel the compound furnishes 6-oxo-l 7a acetoxy-A-nor-B- homoandrostane melting at 114 l C. Optical rotation [0:1 +ll5 (c 0.67). Infra-red spectrum in chloroform: 1,723, 1,692, 1,255 cm. By subsequent hydrolysis this ,product is converted into the known 6- oxo-l7a-hydroxy-A-nor-B-homoandrostane melting at 160 161C; optical rotation [01],, +141(c 0.61

EXAMPLE 250 mg of A -3-oxo-6:l7-diacetoxy-A-nor-B- homoandrostadiene are hydrogenated in 20 ml of henzene with 250 mg of palladium black of 5% strength. The absorption of hydrogen is ml in 20 minutes. After the solution has been freed from the catalyst, it is evaporated under vacuum and the residue is chromatographed on 7 grams of acid alumina (activity 11). 85 mg of crystals are isolated with a lzl-m'ixture of hexane and benzene, which, after two recrystallizations from etherzpentane and sublimation under high vacuum, melt at 139 -l40C. Optical rotation [a],, 1 12 (c 0:49). The compound is'pure 3-oxo-17B- acetoxy-A nor-B-homoandrostane.

EXAMPLE 21 l7B-acetoxy-A-nor-B-homoandrostane which is recrystallized twice from etherl pentane and sublimed in a high vacuum. the melting point is 139 140C. Optical rotation [01],, 1 16 (c 0.43). Infra-red spectrum in chloroformzh 1727, 1258 cm. The compound is identical with the compound described in Example 20.

EXAMPLE 22 EXAMPLE 23 1.5 g of A -3:20dioxo-4:5-oxido-17a-acetoxy pregnene in 500 ml of dioxane are irradiated for 72 hours at 26 to 29C with a low-pressure burner, and the solution is then evaporated under vacuum. The residue is dissolved in 50 ml of alcohol, diluted with 150 ml of ether and agitated in a separating funnel with 10 ml of ice-cold sodium hydroxide solution of 10% strength in 50 ml of water. After exhaustive extraction with so dium hydroxide solution the alkaline extracts are combined and acidified with dilute hydrochloric acid, to yield 850 mg of crude AF3z6z'20-trioxo-l7a-acetoxy-A- nor-B-homopregnene. After recrystallization from methylene chloride+ether the pure compound melts at 198 to 199C. Optical rotation [11],, +76 (c 0.945). In the thin-layer chromatogram (system benzene+methanol 9:1) there appears a single spot.

The share that does not react with sodium hydroxide solution amounts to 0.5 g and is unreacted starting material.

The starting material may be prepared thus:

A solution of 10 g of A-3:20-dioxo-17aacetoxypregnene in 100 ml of methylene chloride and 300 ml of methanol is mixed at 0C dropwise with 60 ml of hydrogen peroxide of 30% strength and 20 ml of sodium hydroxide solution of 10% strength and stirred for 27 hours at 0C. The reaction mixture is then poured into ice water and extracted with methylene chloride and ether. After washing neutral, drying and evaporating under vacuum there are obtained 9 g of crude 3:20-dioxol 7a-acetoxy-4:5-oxidopregnane which is used as it is, without purification, for the following step.

A solution of 5.16 g of crude 3:20-dioxo-17aacetoxy-4:5-oxidopregnane in ml of tertiary amyl alcohol is mixed with 2.5 ml of glacial acetic acid and 0.5 g of mercury, heated to the boil, and a solution of 2.5 g of selenium dioxide in 32 ml of tertiary amyl alcohol is vigorously stirred in dropwise. After 14 hours, the batch is cooled, filtered through a layer of Norite and the filtrate is evaporated under vacuum. The residue is taken up in ethyl acetate and successively washed with potassium iodide solution of 10% strength, sodium thiosulfate solution of 20% strength, sodium carbonate solution of 10% strength and water. On evaporation of the solvent there are obtained 5.78 g of crude A=3:20- dioxo-425-oxido-l7a-acetoxypregnene which, after filtration over alumina (activity 11) and crystallization from methylene chloride-i-ether melts at 203 to 212C.

EXAMPLE 24 '1 g of A=3:6:20-trioXo-17a-acetoxy-A-nor-B- homopregnene in .100 ml of benzene is hydrogenated in the presence of 1 g of palladium carbon of 5% strength. When the amount of hydrogen calculated for 1 mol has been absorbed, the catalyst is filtered off and the filtrate-is evaporated. The residue constitutes 3:6:2-

O-trioxo- 1 7a-acetoxy-A-nor-B-homopregnane. which, after crystallization from ether, melts at 221 224C. Optical rotation [11] +2 (c 0.164).

1n the same manner as described in Example 17, A 3:6-dioxo-l 7a-methy1-l 7fl-hydroxy-A-nor-B- homoandrostene is reduced to 3:6-dioxo-17a-methyll7fi-hydroxy-A-nor-B-homoandrostane melting at 158 160C. Optical rotation [011 =+34 (c 0.921).

EXAMPLE 25 4.15 g of A -3-oxo-4z5-oxido-l7a-methyl-l7fiacetoxyandrostene in 500 ml of dioxane are irradiated for 72 hours at 26 to 30C with a low-pressure burner,

and the batch is then worked up as described in Example 23. The share soluble in sodium hydroxide solution amounts to 3.63 g and constitutes A'-3:6-dioxo-l7amethyl- 1 7B-acetoxy-A-nor-B-homoandrostene which, after recrystallization from methylene chloride-l-ether, melts at 206 210C.

Catalytic reduction of the above product in a ben- EXAMPLE 26 3 g ofA -3-oxo-4:5-oxido-20fl-acetoxypregnene in with a low-pressure burner, and the batch is then worked up as described in Example 23. The share soluble in sodium hydroxide solution yields 2.16 g of Al- 3:6-dioxo-20B-acetoxy-A-nor-B-homopregnene which, after crystallization from methylene chloride-I-ether, melts at 161 163C. Optical rotation in chloroform [01],, +134 (c 0;511).1n addition, 550 mg of starting material are recovered.

The above starting material can be prepared thus:

A-3-oxo-20B-hydroxypregnene (melting at 167 170C) is oxidized with alkaline hydrogen peroxide as described in Example 23, the resulting product is treated with acetic anhydride-lrpyridine, and the 3-oxo- 4:5-oxido-ZOB-acetoxypregniirie so formed is dehydrogenated with selenium dioxide to furnish A 3- oxo-4:5- oxido fl-acetoxypregnene. I

EXAMPLE 27 t v 2 g of A -3:6-dioxo-20fl-acetoxy-A-nor-B- homopregnene'in 50 ml of saturated methanolic potassium carbonate solution areboiled for 32 hours under nitrogen; the batch is then worked up as described in Example 1 1, to yield 1.74 g of crude A-3: 6-dioxo-20flhydroxy-A-nor-B-homopregnene which, after recrysl6 v tallization from methylene chloride-l-ether, melts at 148 149C. Optical rotation [41],, 59 (c 0.937).

EXAMPLE 28 800 mg of A-3:6-dioxo-20fi-hydroxy-A-nor-B- ho'mopregnene in 200 ml of benzene are hydrogenated in the presence of 800 mg of palladium carbon of 5% strength; When the amount of hydrogen calculated'for 1 mol has been abs'orbed,the catalyst is filtered'off and the filtrate is evaporated under. VacuumL The resulting 3:6-dioxo 20BhydroXy-A-nor-B-homopregnane melts at l 17 to 118C after crystallization from ether-I-pentane.

EXAMPLE 29 1.5 g of the lactone of A -3-oxo-4z5-oxide-l7fihydroxy-17a (fl-carboxyethyl)-androstene in 500 m1 of dioxane are irradiated for 72 hours at 26 to 29C with a low-pressureburner; the solution is then evaporated under vacuum and the residue is treated as described in Example 23. The extract obtained with sodium hydroxide solution is the lactone of A -3z6- dioxo-l7flhydroxy-1.7d-(B-carboxyethyl)-A-nor-B- v v I homoandrostene; it melts after recrystallization from methylene chloride-etherat 185 186C, [01],, +85.

Oncatalytic hydrogenation as described in Example 6 the'above product yields the lactone of 3:6-dioxol 7B -hydroxy- 1 7a-(B-carboxyethy1)-A-nor-B homoandrostane which meltsafter recrystallization from methylene chloride-ether at 193.- 194C. The A- nor-'B homo-steroids obtained exhibit also diuretic and antialdosterone actions.

The starting material can bep repared from the lactone of A -3-oxo-l7B-hydroxy-l7a-(B-carboxyethyl)- androstene by oxidation with-hydrogen peroxide and subsequent dehydrogenation with selenium dioxide as described in Example 23. I

1 EXAMPLE 30 Irradiation of I A'-3:20-dioxo4:S-O'Xidopregnene as described in the precedingExamples gives rise to A 3:6:20-trioxo-A-nor-B-homopregnene which, on cata lytic reduction of the double bond in position 1:2, furnishes 3z6:20-trioxo-A-nor-B-homopregnane.

4 The above starting material is accessible from progesterone by epoxidation and dehydrogenation with selenium dioxide as described in Example 23.

EXAMP E 31 7 When the undermentioned starting materials .ob-

' tained from the corresponding A1-3-ketones as described-in Example 23 are irradiated, there are obtained-the irradiation products shown under B below:

A.St ar1ing material .-1 I

Al-3-oxo-4:Spxidocholestene j cholestene.

-'-, homospirostene.

EXAMPLE 32 dium hydroxide solution'and the extract acidified with EXAMPLE 33 1.5 grams of A -3-oxo-4:5-oxido-7a-methyl-17B- acetoxy-androstene in 500 cc of dioxane are irradiated as described in Example 23, A -3z6-dioxo-7aa-methyl- 17/3-acetoxy-A-nor-B-homo-androstene being obtained.

in an analogous manner A3-oxo-4:5-oxido-7a:17a-

A dimethyl-17p-hydroxy-androstene is converted into A -3 :6-dioxo-7aa 17B-dimethyl-17,8-hydroxy-A-norf B-homo-androstene.

A -3-oxo-4:5-oxido-7a-methyl-17fi-acetoxyandrostene and ,A-3-oxo-4:5-oxido 7a:l7a-dimethyl- 17B-hydroxy-androstene are obtained, for example, by reacting A 3 -oxo-7a-methyl-17fl-acetoxyandrostadiene and A'=-3-oxo-7a:170Edimethyl-17B- hydroxy-androstadiene, respectively, with perbenzoic acid as described in Example 1.

EXAMPLE 34 In the catalytic hydrogenation according to Example 6 there are obtained from the compounds listed under A the hydrogenation products listed under B A. Starting materials A'-3:6:20-trioxo 1 7acapronyloxy-A-nor-B- homo-pregnene A'-3:6:20-trioxo-l7amethyl-A-nor-B-homopregnene A-3:6-dioxo-7aa-methyll7B-acetoxy-A-nor-B- B. Hydrogenation products 3:6:20-trioxo-17a-capronyloxyA-nor-B-homo-pregnane 3:6:20-trioxo-17a-methyl- A-nor-B-homo-pregnane 3:6-dioxo-7aa-methyl-17B- acetoxy-A-nor-B-homohomo-androstene androstane A '3:6-dioxo-7aa:17a- 3:6-dioxo-7aa dimethyldlmethyl'l 7fi-hydroxy- 1 7fl-hydroxy-A-nor-B-homo- A-nor-B-homo-androstene androstane.

EXAMPLE 35 1.5 grams of A-3:20-dioxo-4z5-oxido-1lfizl'la-dihydroxy-21-acetoxy-pregnene are irradiated and worked up as described in Example 23, A -3:620 trioxo-l 15:1 7a-di-hydroxy-21-acetoxy-A-nor-B-homopregnene being obtained and A'-3:6:20-trioxo- 1 1 B: l 711:2 l trihydroxy-A-nor-B-homopregnene formed by partial hydrolysis during extraction with so dium hydroxide solution.

I of perbenzoic acid in 100 cc of chloroform (45 mg/cc) for 7 days in the dark at room temperature. The reaction solution is then diluted with ether and washed in succession with aqueous potassium iodide and sodium thiosulfate solution, water, sodium bicarbonate solution and again with water. After evaporation, 1.4 grams of a mixture containing 17:20;20:2l-bismethylenedioxy derivative of 4a:5aand 4B:5B-oxidoprednisolone are obtained.

1.4 grams of the above mixture are irradiated in 170 cc of dioxane for 14 hours with a low pressure mercury lamp. After working up as described in Example 23, 420 mg of 17:20;20:2l-bis-methylenedioxy derivative of A'-3:6:20-trioxo-1 1B: 1 701:2 1 -trihydroxy-A-nor-B- homo-pregnene are obtained; after filtration over silica gel, decoloration with animal charcoal and crystallization from a mixture of acetone and petroleum ether, the product melts at 210 230C with decomposition; optical rotation [01],, --7 (0 0.7). Ultra-violet spectrumzk 236 and 310 mp. respectively, (e 8000 and 6080 respectively).

EXAMPLE- 37 v V A solution of 500 mg of the 21-acetate of'A-4,5- oxide-17dz,21-dihydroxy 3 ,1 1 ,20-trioxopreg'nene melting at2l4 4 218C) in 125 ml of dioxane is irradiated for 40 hours with a mercury vapour low-pressure burner while being stirred with a magnetic stirrer under a current of nitrogen at 27 30C. The solvent is then evaporated under vacuum and the residue taken up in a 1:2-mixture of alcohol and ether and agitated in a separating funnel three times with ice-cold l sodium hydroxide solution. The sodium hydroxide extract is acidified with dilute hydrochloric acid, axtracted with methylene chloride and evaporated, to yield 310 mg of crude A -3,6,l 1,20-tetraoxo-l 7,2 l -dihydroxy-A-nor- B-homopregnene. (The 21-acetate is hydrolysed during the working up). The product is purified by chromatography on 30 times its own weight of silica gel. Elution with benzene and with benzene+ether yields about 60 mg of oily products; elution with ether furnishes the pure compound which, after having been recrystallised from methylene chloride+ether, melts at 184 186C.

To prepare the starting material 4.14 g of crude 21-acetate of 4,5 -oxido-3,1 1,20-trioxo- 1 711,2 1-

, dihydroxy-pregnane (cf. Journal -of'the American As described in Example tithe above irradiation EXAMPLE 36 I 1.8 grams of l7:20;20:2l-bis-methylenedioxy derivative of prednisolone are allowed to stand in a solution Chemical Society 79, page 3,596 [1957] are dissolved in 60ml of amylene hydrate. 2 ml of glacial acetic acid and 0.4 g of mercury are then added and the batch is stirred and heated to the boil, and 25 ml of amylene hydrate containing 2 g of selenium dioxide are dropped in. After 14 hoursthe batch is cooled, the amylene hydrate evaporated under vacuum, the residue taken up in ether and washed successively with sodium thiosulphate and sodium bicarbonate solution and then with water, dried and evaporated. The residue is chromato- EXAMPLE 3s A solution of 165 mg of A-3-oxo-4B,5-oxido-17B- acetoxy-l -methylandrostene in 65 ml of dioxane is irradiated with a mercury vapour low-pressure burner (254mg) for 2 hours and then evaporated under vacuum. The crystalline residue is twice recrystallised from aqueous methanol, whereupon it melts at 132C, and is A3,6-dioxo-l7B-acetoxy-l-methyl-A-nor-B- homo-androstene or A- -3-oxo-6-hydroxy-17B- acetoxyl -methy1-A-nor-B-homo-androstadiene respectively. For analysis a specimen is sublimed in a high vacuum at 125C. Optical rotation [a],, +34 (c 0.61 in chloroform). Infrared spectrumzv 1,725, 1,660, 1,612, 1,255 cm (in chloroform). Ultraviolet spectrumzh 249mg. (e 9,980), 311mg. (6 6,600 in ethanol).

The starting material is prepared as follows:

100 mg of A--3-oxo-l7fl-hydroxy-1- methylandrostadiene are acetylated for 4 hours at 50C in 5 ml of a lzl-mixture of acetic anhydride and pyridine. The batch is evaporated under vacuum and the crude product is dissolved in benzene+ether 9:1 and filtered through neutral alumina of activity III. On evaporation of the solvent there results the crude A 3-oxo-17B-acetoxy-1-methylandrostadiene. After having been twice recrystallised from acetone-l-petroleum ether the pure compound melts at 141 142C. Optical rotation [04],, =-l0 (c 0.53 in chloroform). Infrared spectrum in chloroform: 1,722, 1,657, 1,615, 1,255 cm". Ultraviolet spectrum: m 253mg 21,500 in ethanol).

612 mg of the above acetate in a solution of 400 mg of perbenzoic acid in ml of chloroform is kept for 4 days in the dark at room temperature. The reaction solution is diluted with ether and successively washed with aqueous potassium iodide, sodium thiosulphate and sodium bicarbonate solution and with water. The solvent is evaporated under vacuum and the resulting crude product is chromatographed on neutral alumina of activity 11. Benzene and a 9:1-mixture of benzene and ether elute 332 mg of crystalline A-3-oxo-4,65,- oxido-l7B-acetoxy-1-methylandrostene which melts at 168 169C after two recrystallisations from acetone+petroleum ether. Optical rotation [a +170 (c 0.98 in chloroform). Infrared spectrum in chloroform:v,,,,,,=1,725, 1,670, 1,616, 1,255 cm. Ultraviolet spectrurnzlt 249mA (e 9970 in ethanol). 1

EXAMPLE 39 350 mg of A-3-oxo-4,5-oxido-17B-acetoxy-oestrene in 70 ml of dioxane are irradiated for 3hours with a mercury vapour low-pressure burner, and the solution is then evaporated under vacuum. The residue is taken up in ether and the ethereal solution washed with icecold 2N-sodium hydroxide solution. The basic equeous extracts are immediately acidified with dilute sulphuric acid and then extracted with ether. The resulting organic phase is washed with water until neutral, dried and evaporated, to leave 200 mg of crystalline photoproduct, namely A-3,6-dioxo-l7B-acetoxy-A-nor-B-- -homo-oestrene or A -3-oxo-6-hydroxy-l7fl-acetoxy- A-nor-B-homo-oestradiene respectively. For purification the product is treated for a short time in benzene with active carbon and then dissolved in a 9:1-mixture of benzene and ether and filtered through neutral silica gel. After having been recrystallised three times from methylene chloride+methanol the product melts at 171 172C. Optical rotation [a],, +154 (c 0.65 in chloroform). Infrared spectrum:v,,,,, 1,722, 1,666, 1,610, 1,255 cm. Ultraviolet spectrum: u 238mg. (6 6,800);)\,,,,, 309m (6 6,480 in ethanol).

The starting material is prepared as follows:

A mixture of 500 mg of 3-oxo-4,5-oxido-17B- acetoxy-oestrane, 25 ml of a 10:'1-solution of tertiary butanol and glacial acetic acid and 500 mg of seleium dioxide is stirred for 2 hours and heated at the boil. The cooled solution is filtered and then evaporated under vacuum. The residue is dissolved in ethyl acetate and filtered through Celite. The ethyl acetate solution is then successively washed with ammonium hydrosulphide solution, ammonia, dilute sulphuric acid and with water. The oil obtained by evaporation of the solvent is taken up in benzene and treated for a short time with active carbon. The solution is freed from the active carbon and evaporated. The resulting product is dissolved in a 9:1-mixture of benzene and ether and filtered through neutral alumina of activity 111, to yield 350 mg of amorphous A-3-oxo-4,5 -oxi do- 1 7B-acetoxyoestrene. Infrared spectrum in chloroformzv 1,725 1,680, 1,620 cm.

EXAMPLE 40 700 mg of 3-oxo-4,5-oxido-l7B-acetoxy-oestrane in 200 ml of dioxane are irradiated for 2 hours with a mercury vapour high-pressure burner. The solution is then evaporated under vacuum and the residue chromatographed on 60 times its own weight of neutral silica gel. A 9:1-mixture of benzene and ether elutes 598 mg of 3 ,6-dioxo-17B-acetoxy-A-nor-B-homo-10-oestrane or A -3-oxo-6-hydroxy-l7B-acetoxy-A-nor-B-homo-10;- oestrene respectively. AFter two recrystallisations from methylene choride+methanol the product melts at 152- C. Optical rotation [11],, +62 (c 0.85 in chloroform). Infrared spectrum in chloroformzv 1,720, 1,642, 1,605, 1,260 cm". Ultraviolet spectrum: A 292mg. (e= 5,900 in ethanol); e 311ms(e=9,850 in 0.01 N-potassium hydroxide solution in ethanol).

The starting material is prepared as follows:

While being stirred at 15C 2 ml of aqueous 4N- sodium hydroxide solution and then 2 ml of perhydrol of 30% strength are added to 1' g of l9-nortestosterone in 60 ml. The batch is kept for 4 hours at 4C, then diluted with ethyl acetate and washed with water until neutral. The solution is evaporated under vacuum and the resulting amorphous residue is acetylated in 20 ml of a lzl-mixture of acetic anhydride and pyridine overnight at room temperature. The crude product obtained by evaporation under vacuum is dissolved in benzene and filtered through neutral alumina of activity 11. One crystallisation of the filter residue from acetone+petroleum ether yields 750 mg of 3-oxo-4,5- oxido-l7B-acetoxy-oestrane.melting at 102C. A specimen recrystallised three times melts at 104C. Optical rotation [01],, +48 (c 0.43 in chloroform). Infrared spectrumzv 1725 1700 (broad), 1255 cm (in chloroform).

EXAMPLE 41 500 mg of 3-oxo-4,5-oxido-l7B-hydroxy-7aa,17adimethyl-oestrane (melting at 138 140C after recrystallisation from ether) in ml of dioxane are irradiated for 13 hours with a mercury vapour high-pressure burner. The solution is then evaporated under vacuum and the residue dissolved in a 4:1-mixture of benzene and ether and filtered through neutral silica gel, to yield 400 mg of 3,6-dioxo-l7B-hydroxy7aa5l7a-dimethyl- A-nor-B-homo-oestrane or A -3-oxo-6,17B-dihydroxy- 7aa,17a-dimethyl-A-nor-B-homo-oestrene respectively which, after one recrystallisation from aqueous methanol, melts at 168 169C. Optical rotation [41] +83 (c 0.67 in chloroform). Infrared spectrum in chloroformzu 3,550, 1,640, 1,595 cm. Ultraviolet spectrumzx 293 my. (6 9,380).

In an analogous manner the following starting materials yield the corresponding A-nor-B-homosteroids:

Starting material A-nor-B-homo compound 3-oxo-4,5-oxidol 7fl-hydroxy- 7aa, l 7a-dimethylandrostane (m.p. l54lS6C, from isopropyl ether) 3,6-dioxo-l7fi-hydroxy-7aa,17a-

dimethyl-A-nor-B- homoandrostane or respectively A-"-3-oxo-6,l7B-dihydroxy- 72111, 1 7a-dimethyl-A-nor-B- homo-androstene (m.p.

162l63C, from isopropyl ether).

3-oxo-4,5-oxidol 7B-hydroxy- 1 7aethinyloestrane (amorphous) 3,6-dioxo-l7fi-hydroxy-17aethinyl-A'nor-B-homo-oestrane or respectively A"-3-oxo-6,l7B'dihydroxy-17aethinyl-A-nor-B-homo-oestrene (m.p. 153158C, from ether).

3-oxo-4,5-oxido-l7B-hydroxy-17aethinylandrostane (m.p. 168-174C, from 14 chloride+ether) 3 ,6-di0xo-17B-hydroxy-17aethinyl-A-nor-B- homoandrostane or A E-0x06, l 7fl-dihydroxy- 1 7aethinyl-A-nor-B- homoandrostene (m.p. 166168C, from methylene chloride-tether).

3-oxo-4,5-oxido-1 7B-acet0xy- 17aethinylandrostane (m.p. 168- 1 74C) 3 ,6-dioxo- 1 7fi-acetoxyl 701- ethinyl-A-nor-B homoandrostane and A-3-oxo-6-hydroxy- 1 7pacetoxyl 7a-ethinyl-A-nor-B homoandrostene (m.p. l76-l82C, from methylene chloride+ether) 3-oxo-4,5-oxido-17B- decanoyloxyoestrane (oil) 3,6-dioxo-17fl-decanoyloxy-A- nor-B-homo-oestrane and A"-3-oxo-6-hydroxy-17B- decanoyloxy-A-nor-B-homooestrene (m.p. 5051C, from pentane) 3-oxo4,5-oxido- 1 7fi-(B- phenylpropionyloxy)-oestrane (m.p. 131-134C) 3,6-dioxo-17B-(B- phenylpropionyloxy)-A-nor-B- homo-oestrane and A -3-oxo-6-hydroxy-173-(3- henylpropionyloxy )-A-nor-B- omo-oestrene (m.p. 98-99C,

from ether+pentane) 3,6-dioxo-l 7fl-hydroxyl 70:-

methyl-A-nor-B-homo-oestrane 3-oxo-4,5-oxidol 7B-hydroxy- 1 7amethylocatrane valerianyloxy-A-nor-B-homoandrostene (m.p. 91C, from ether-l-pentane) 3-oxo-4,5 -oxido- 1 7B- undecenoyloxy-androstane 3 ,o-dioxol 7fi-undcccnoyloxy-A- nor-B-homoandrostanc and A-3-oxo-6-hyd roxy- 1 7B undecenoyloxy-A-nor-B- homoandrostene (m.p. 51 52C, from pentane) 3-oxo-4,5-oxido-7aa, 1 7adimethylandrostane (m.p'.

homoandrostene (m.p.

l62-164C) 3oxo-4,5-oxido-20-ethylenedioxy' pregnane (m.p. 2l7-223C) A-3-oxo-6-hydroxy-20- ethylenedioxy-A-nor-B- homopregnene (m.p. -16lC); A"'-3,20-dioxo-6-hydroxy-A- nor-B-homopregnene (m.p. 137-l38C);

A -3 ,20-dioxo-6-acetoxy-A- nor-B-homopregnene (m.p. 95-97C).

A The above starting materials are prepared from the corresponding A-3-keto'nes by the method described in Example 40.

EXAMPLE 42 EXAMPLE 43 3.45 g of 3-oxo-4,5-oxido-20-ethylenedioxy-Z1- acetoxypregnane in 255 ml of dioxane are irradiated for 13 hours with a high-pressure burner at a temperature of 17 to 18C. The solution is then evaporated, to leave as residue crude 3,6-dioxo-20-ethylenedioxy-21- acetoxy-A-nor-B-homopregnane; to purify it, it is dissolved in methylene chloride and chromatographed on silica gel (containing 5% of moisture). The residue of the methylene chloride eluates is recrystallized from methanol to yield the pure product melting at 126 131C. The mother liquor is evaporated, and the residue is dissolved in 60 ml of methanol, mixed with a solution of 1 g of potassium carbonate in 20 ml of water and hydrolyzed by being boiled for 2 hours under reflux. The solution is evaporated under vacuum and the residue agitated with ethyl acetate. The ethyl acetate solutions are combined, washed with water, dried and evaporated under vacuum. To purify the hydrolysis product the residue is taken up in a 1:3-mixture of methylene chloride and ether and repeatedly agitated with ice-cold 2N-sodium hydroxide solution. The combined sodium hydroxide extracts are adjusted at 0C with phosphoric acid to pH 4 to 5 and exhaustively extracted with methylene chloride. The methylene chloride solutions are washed with water, dried and evaporated under vacuum. After repeated recrystallization from a mixture of methylene chloride and isopropyl ether there are obtained 1.56 g of pure 3,6- dioxo-20-ethylene-dioxy-2 l -hydroxy-A-nor-B-homopregnane melting at 164 165C.

1 g of the latter compound is shaken with 20 ml of oxygen-free 70% formic acid (deaerated at 100C with nitrogen) for 20 minutes under nitrogen at 60C. The resulting solution is mixed at C with a solution of 34 g of potassium bicarbonatein 200 ml of water and exhaustively extracted by agitation with methylene chloride. The combined methylene chloride solutions are washed with water, dried and chromatographed on 20 g of silica gel (containing of moisture). The considerably concentrated methylene chloride eluates are mixed with isopropyl ether, whereupon 3,6,20-trioxo- 2l-hydroxy-A-nor-B-homopregnane crystallizes out; it melts at 132 136C. Yield: 710 mg.

The starting material used above is obtained from the known A -3,20-bisethylenedioxy-2 l -acetoxypregnene by partial deketalization in 3-position with a mixture of paratoluenesulfonic acid and acetic acid in acetone. The resulting monoketal is mixed with hydrogen peroxide in the presence of alkali and the hydrolyzed 21- acetoxy group is finally reacetylated with acetic anhydride in the presence of pyridine.

Irradiation as described above may also be performed with 3-oxo-4,5-0xido-20-ethylenedioxy-21- hydroxypregnane, whereupon 3,6-dioxo-- ethylenedioxy-21-hydr0xy-A-nor-B-hompregnane is obtained as irradiation product.

EXAMPLE 44 5 g of 3-Oxo-4,5-oxido-20-ethylenedioxypregnane in 900 ml of dioxane are irradiated for 48 hours with a high-pressure burner at 17 to 18C. The solution is evaporated and the residue dissolved in a 1:3-mixture of methylene chloride and ether, and the solution is repeatedly agitated with ice-cold 8% sodium hydroxide solution. The combined sodium hydroxide extracts are mixed at 0C with phosphoric acid to pH 4 to 5 and the whole is exhaustively extracted with methylene chloride. The methylene chloride extracts are washed with water, dried and evaporated under vacuum. On addition of ethanol and further evaporation of the methylene chloride, 3,6-dioxo-20-ethylenedioxyA- nor-B-homo-pregnane crystallizes out. Recrystallization from a mixture of methylene chloride and isopropyl ether furnishes 2.2 g of the pure compound melting at 160 to 162C.

2 g of the compound thus obtained are mixed with 30 ml of 80% acetic acid and heated for 30 minutes on a boiling water bath. The solution is then evaporated under vacuum, the residue is dissolved in a 1:3-mixture of methylene chloride and ether, and the solution is washed with water, dried and evaporated under vacuum. The residue is dissolved in methylene chloride and chromatographed on 20 g of silica gel (containing 5% of moisture). Themethylene chloride solutions are evaporated and the residue is recrystallized from a mixture of methylene chloride and isopropyl ether, to yield 1.6 g of 3,6,20-trioxo-A-nor-B-homopregnane melting at 137 138C.

l g of the last-mentioned compound is dissolved in 2 ml of pyridine, 2 ml of acetic anhydride are added and the whole is kept for 4 days at room temperature. The solution is then mixed with ice, kept for 1 hour at 20C and evaporated under vacuum. The residue is chromatographed first with methylene chloride and then with a 99:1-mixture of methylene chloride and tertiary butanol on 20 g of silica gel; the first methylene chloride fractions may still contain some starting material.

The further fractions eluted with methylene chloride and a 99:1-mixture of methylene chloride and tertiary butanol are combined and evaporated. The residue is recrystallized from hexane+pentane, to yield 800 mg of A -3,20-dioxo-6-acet0xy-A-nor-B-homopregnene melt ing at 95 to 97C.

The above-mentioned starting material is accessible from the known A -3B-acetoxy-2O-ethylenedioxypregnene by alkaline hydrolysis, oxidation of the resulting A -3-hydroxy-compound with chromium trioxide to A 3-oxo-20-ethylene-dioxy-pregnene, followed by treatment with hydrogen peroxide in the presence of sodium hydroxide solution.

EXAMPLE 45 700 mg of 3-oxo-4,5-oxido-l6a,l7a-dihydroxy-20- ethylenedioxypregnane in 140 ml of dioxane are irradiated for 13 hours with a high-pressure burner at 20C. The solution is evaporated and the residue dissolved in ether and repeatedly agitated with ice-cold 2% sodium hydroxide solution. The aqueous extracts are combined, adjusted at 0C with phosphoric acid to pH 4 to 5 and exhaustively extracted by agitation with methylene chloride. The methylene chloride solutions are combined, washed with water, dried and evaporated under vacuum. The resulting 3,6-dioxo-l6a, l7a-dihydroxy-20-ethylenedioxy-A-nor-B- homopregnane (360 mg) is dissolved in 30 ml of pure acetone, heated to a gentle boil, mixed with 3 drops of concentrated hydrochloric acid, heated for another 2 minutes and then kept for 24 hours at 20C. On dilution with ice water there are obtained crystals which are suctioned off and dried. For purification they are dissolved in methylene chloride and chromatographed on 2 g of silica gel (containing 5% of moisture). The residue from the methylene chloride eluates is recrystallized from methylene chloride+isopropyl ether, to yield 280 mg of 3,6,2O-trioxo-1611,17a-dihydroxy-A-nor-B- homopregnane-l6,l7-acetonide melting at 204 to 205C.

The starting material used above is obtained from A -3B-acetoxy-2O-ethylenedioxypregnadiene by alkaline hydrolysis and Oppenauer oxidation to A"-3-ox0- 20-ethylenedioxypregnadiene, oxidation with hydrogen peroxide to the corresponding 4,5-oxido compound, followed by hydroxylation of the 16,17-double bond with osmium tetroxide.

EXAMPLE 46 A solution of 2.168 g of 3-oxo-4,5-oxido-l 1B- hydroxyl 7d,20;20,2 l -bismethylenedioxypregnane (mixture of the 4a,5aand 4B,5B-oxido compounds) in 500 ml of pure dioxane is vigorously stirred at 18 to 22C while being irradiated with a mercury vapour high-pressure lamp until a specimen of the reaction mixture reveals that the infrared absorption has reached a maximum at 6.08 and 6.24p.. This is generally the case after 8 to 16 hours. The solution is then benzene+ethyl acetate (85:15) fractions. The crystalline evaporation residues yield after recrystallization from methylene chloride+ether a total of 0.967 g of 3,- 6-dioxo-l lB-hydroxy-l7a,20;20,2 l bismethylenedioxy-A-nor-B-homopregnane in colorless, coarse rhombohedrons melting at 193 196C.

To eliminate the protective groups in the side chain, a solution of 0.420 g of 3,6-dioxo-1 lB-hydroxy- 17a,20;20,2 l bismethylenedioxy-A-nor-B- homopregnane in 25 ml of tetrahydrofuran is mixed at 15C within 30 minutes with 75 ml of 2.66-molar aqueous perchloric acid. The solution is stirred for 16 hours at 20C, then cooled with ice and neutralized with 250 ml of N-sodium bicarbonate solution and the hydrolysis product is agitated with methylene chloride+ether 1:2). The extracts are washed with 0.4N-sodium bicarbonate solution and with water, dried over sodium sulfate and evaporated to yield 0.372 g of a crystalline crude product; for purification it is dissolved in 100 ml of benzene and the solution is filtered through a column of 10 g of silica gel prepared with benzene, while being further eluted with benzene+ethyl acetate mixtures 95:5, 85:15 and 50:50. On evaporation under vacuum the filtrates are extensively freed from benzene and ethyl acetate and yield a total of 0.315 of pure 3,6,- 20-trioxo-1 13,1711,2l-trihydroxy-A-nor-B- homopregnane in almost colorless crystals melting at 137 138/176 178C.

When the l7,20;20,2l-bismethylenedioxy group is split with 70% perchloric acid in glacial acetic acid at room temperature (2-3 hours), A -3,20-dioxo-6- acetoxy-l 13,1701,21trihydroxy-A-nor-B- homopregnene is obtained, in addition to the corresponding ZI-acetate, which can be hydrolyzed as described above with dilute perchloric acid in tetrahydrofuran to 3,6,20-trioxo-1 113,1 701,2l-trihydroxy-Amor-B- homopregnane and to its 21-acetate respectively.

The starting material used in the above Example can be prepared as follows:

In the course of 30 minutes, at 15 to 20C, 62.5 ml of N-aqueous tetramethylammonium hydroxide and 31.25 ml of 30% hydrogen peroxide are added simultaneously with stirring from two separate dropping funnels to a solution of 2.528 g of A -3-oxo-l lB-hydroxy- 17a.,20;20,2lbismethylenedioxy-pregnene in 532 ml of methanol previously cooled to l5C. After having kept the solution for 24 hours at 10C, the alkali is neutralized at C with 62.5 ml of 1.5N-orthophosphoric acid; the-reaction solution is poured over a mixture of 250 g of ice and 500 ml of ice-cold water and extracted by agitation with ice-cold methylene chloride. The ice-cold extracts are washed with water,

pregnene 3 ,6-dioxol 7a,20;20,2 l

bismethylenedioxy-A-nor-B- homo-A regnene (m.p.

224"-226Cl 3,20-diox0-6.2 1 -diacetoxy-1 3,1 1,20-trioxo-6,2l-diacetoxy- 17a-hydroxy-A-nor-B-homo- A -pregnadiene.

1,000 Tablets each containing 5 mg of the active substance. Ingredients:

3 ,6,20-trioxo-l 7B-acetoxy-A-nor-B-homopregnane 5.0 lactose 70.0 gelatine 3.0

20 wheat starch 40.0 arrowroot 15.0 magnesium stearate 0.7 talc 6.3

Procedure:

The mixture of the active ingredient, lactose and wheat starch is moistened with a gelatine solution of 10% strength to form a slightly plastic mass, and then granulated in the usual manner. After being dried at 40C, the mass is brought into the usual grain size by being passed through a sieve. Arrowroot, magnesium stearate and talc are added to the dried mass and the mixture is then compressed into tablets of 7 mm in diameter.

EXAMPLE 48 1,000 Tablets each containing 1 mg of the active substance. Ingredients:

A -3 :6:20-Trioxol 7B-acetoxy-A-nor-B-homopregnene 1 .0 lactose 53 .0 gelatine 1 .0 wheat starch 39.5 magnesium stearate 0.3 tale 5 .2

Procedure: analogous to that described in Example 47.

EXAMPLE 49 1,000 Tablets each containing 1 mg of the active sub- 50 stance. Ingredients:

A -3z6-Dioxo-l 7a-methyll 7B-methyl-l 7B- hydroxy A-nor-B-homo-androstene lactose colloidal silicic acid with hydrolysed starch .wheat starch arrowroot magnesium atearate talc LII

EXAMPLE 50 In the manner described in Examples 47 to 49 tablets can be prepared each containing 25 mg of the lactone of A-3:6-dioxo-l7B-hydroxy-17a-(B-carboxy-ethyl)- A-nor-B-homo-androstene or 1 to 5 mg of the active products described in the following Examples.

Procedure: analogous to that-described in Example 47.

EXAMPLE 51 l,000 Linguettes each containing 1 mg of the active substance. Ingredients:

A'-3:6:20Trioxo-l 113: 175:2 l-trihydroxy-A- nor-B-homo-pregnene 1 g lactose 100 g saccharose 229 g stearic acid 3 g talc 17 g Procedure:

The mixture of the active substance with lactose is moistened with an aqueous solution of saccharose and granulated in the usual manner. After being dried, the sieved granulate is mixed with stearic acid and talc and then compressed into linguettes.

EXAMPLE 52 100 Oil ampoules each containing 25 mg/ml of the active substance. Ingredients:

3:6-Dioxo-l 7B-acetoxy-A-nor-B-homoandrostane 2.5 g benzyl alcohol 10 ml sesame oil 90 ml Procedure:

The active ingredient is dissolved in benzyl alcohol and the stirred solution diluted with hot sterilized sesame oil. 1 ml of this solution containing the ingredients in the above given amounts is filled in ampoules which are sterilized at 160C for 1.5 hours.

EXAMPLE 53 100 Oil ampoules each containing 10 mg/ml of the active substance. Ingredients:

androstene neutral sterilized sesame oil 100 m Procedure:

In a 100 ml flask the active substance is dissolved in 5 to ml of pure acetone and the acetone evaporated. The residue is then dissolved in the sesame oil which has been purified and sterilized by heating it to 180C for two hours. The solution obtained is filtered through a glass filter and 1 ml of the filtrate is filled in ampoules which are sterilized at 160C for L5 hours.

EXAMPLE 54 in the manner described in Examples 52 and 53 oil ampoules can be prepared each containing 10 to 25 mg of Ai -3 -oxo-6: l 7B-diacetoxy-A-nor-B-homoandrostadiene, A-3:6-dioxo-l7B-acetoxy-l9-nor-A- nor-B-homo-androstene, A-3:6:20-trioxo-l7acapronyloxy-A-nor-B-homo-pregnene or 3:6-dioxo- 7aa-methyli 7fl-acetoxy-A-nor-B-homo-androstane.

EXAMPLE 55 1,000 Tablets of an anabolic preparation containing 3 ,o-dioxo-l 7/3-hydroxy-7aa l 7a-dimethyl-A-nor-B- homo-oestrane are manufactured from the following ingredients:

' grams 3,6-dioxol 7B-hdroxy-7aa, 1 7adimethyl-A-nor- -homo-oestrane l.0 lactose 74.0 gelatine 3 .0 wheat starch 40.0 arrowroot 15.0

magnesium stearate 0.7 talcum 6.3

140.0 grams Formulation:

grams I dimethyl-A-nor-B-homo-oestrane 0. l lactose 50.0 colloidal silicic acid with hydrolysed starch 5.0 arrowroot 4 9.0 wheat starch 20.9 magnesium stearate I 0.7 talc 4.3

90.0 grams The tablets are made in a manner similar to that set forth above.

For parenteral use there are especially suitable oil ampoules as follows:

Oil ampoules each containing 0.05 mg/ml of the active substance. Ingredients:

3,6-Dioxo-l7fi-hydroxy-7aa,l7adimethyl-A-nor-B-homo-oestrane 0.005 gram neutral sesame oil 100 ml They are prepared in a manner similar to that set forth in previous Examples.

In an analogous manner anabolic preparations containing 3,6-dioxo-l7B-hydroxy-7aa,17a-dimethyl-A- nor-B-homoandrostene can be manufactured.

EXAMPLE 56 100 Oil ampoules of an anabolic preparation for parenteral administration, each containing 25 mg per ml of A'-3,6-dioxo-l7B-acetoxy-l-methyl-A-nor-B-homoandrostene are manufactured from the following ingredients:

A-3,6dioxol 7B-acetoxy- 1 -methyl- A-nor-B-homo-androstene 2.5 g benzyl alcohol l0 ml sesame oil 90 ml The active principle is dissolved in the benzyl alcohol and the stirred solution is diluted with sesame oil sterilised at an elevated temperature. 1 ml of this solution, which contains the above proportions of the ingredients, is charged into ampoules which are then sterilised for l '12 hours at C.

in an analogous manner anabolic preparations can be prepared which are suitable for parenteral administration and contain as active principle A-3,6-dioxo-17B- acetoxy-A-nor-B-homo-oestrene or 3,6-dioxo-17B- acetoxy-A-nor-B-homol 0-oestrane.

EXAMPLE 57 1000 Tablets of a gestagenic pharmaceutical preparation each containing mg of 3,6-dioxo-l7B-hydroxy- 17a-ethinyl-A-nor-B-homo-oestrane are manufactured from the following ingredients:

As described in Example 55.

In an analogous manner gestagenic preparations for oral administration, containing 3,6-dioxo-l7fihydroxy-17a-ethinyl-A-nor-B-homoandrostane as active principle, can be manufactured.

EXAMPLE 58 1,000 Tablets of a pharmaceutical preparation for use as an antiphlogistic, each containing 1 mg of A 3 ,6,1 l, ZO-tetraoxo- 1 701,2 1 -dihydroxy-A-nor-B- homopregnene, are manufactured from the following ingredients:

A'-3,6,l l,20-tetraoxo- 1 701,2 1 -dihydroxy-A-nor-B-homopregnene lactose gelatine wheat starch magnesium stearate talcum Formulation:

As described in Example 55.

EXAMPLE 59 1,000 Tablets of an anabolic preparation each containing 5 mg of 3,6-dioxo-l7B-hydroxy-l7a-methyl-A- nor-B-homo-androstane are manufactured from the following ingredients:

grams 3 ,6-dioxo-17fl-hydroxy-17a-methyl- A-nor-B-homo-androstane 5.0 lactose -70.0 gelatine 3.0 wheat starch 40.0 arrowroot 15.0 magnesium stearate 0.7 talcum 6.3 140.0 The manufacture is similar to that described in Example 57.

We claim: 1. A compound having the formula W a H ,7 my- EH73:

in which R stands for a member of the group consisting of =H, and =0, R, for a member of the group consisting of =0, =H

2011 on O-abyl O-aeyl and E 811 H \H wherein the acyl radical is that of an acid selected from the group consisting of formic, acetic, propionic, butyric, trimethylacetic, caproic, valeric, oenanthic, decanoic, undecylenoic, cyclopentyl proprionic, hexahy drobenzoic, phenylpropionic, benzoic, furoic, trifluo- I roacetic, ethyl carbonic and methyl carbonic acids. R

and R, for a member of the group consisting of H,

1 lower alkyl and O-R, R together with R, a member of the group consisting of R for a member of the group consisting of =0,

lower alkylene,

R for a member of the group consisting of -H and -O-R and R for a member of the group consisting of -H, an acyl radical wherein the acyl radical is that of an acid selected from the group consisting of formic, acetic, propionic, butyric, trimethylacetic, caproic, valeric, oenanthic, decanoic, undecylenoic, cyclopentyl proprionic, hexahydrobenzoic, phenylpropionic, benzoic, furoic, trifluoroacetic, ethyl carbonic and methyl carbonic acids. and methyl ethyl, propyl, benzyl, cyclopentyl and tetrahydropyranyl, and X is a member of the group consisting of hydrogen and methyl, the corresponding l-dehydro compounds the enol esters of acids selected from the group consisting of acetic, propionic, butyric, benzoic, and para-toluenesulfonic acids and the lower alkyl enol ethers and thioethers thereof, with the proviso that R be different from acyl in R and R when taken together.

2. 3,6,20-Trioxo-A-nor-B-homo-pregnane.

3. 3,6,20-Trioxo-17a-hydroxy-A-nor-B-homopregnane.

4. A -3,6,20-Trioxo-A-nor-B-homo-pregnene.

5. A-3 ,6,20-Trioxol 7a-hydroxy-A-nor-B-homopregnene.

6. A -3,6;l 1,20-Tetraoxo- 1 711,2 1 -dihydroxy-A-nor- B'-homo-pregnene.

A-3,6;l 1,20-Tetraoxo-7a-methyl- 1 701,2 1-

dihydroxy-A-nor-B-homo-pregnene.

8. A'-3 ,6,20-Trioxo-1 15,1 704,2 l-trihydroxy-A-nor-B- homo-pregnene. 

2. 3,6,20-Trioxo-A-nor-B-homo-pregnane.
 3. 3,6,20-Trioxo-17 Alpha -hydroxy-A-nor-B-homo-pregnane.
 4. Delta 1-3,6,20-Trioxo-A-nor-B-homo-pregnene.
 5. Delta 1-3,6,20-Trioxo-17 Alpha -hydroxy-A-nor-B-homo-pregnene.
 6. Delta 1-3,6;11,20-Tetraoxo-17 Alpha ,21-dihydroxy-A-nor-B-homo-pregnene.
 7. Delta 1-3,6;11,20-Tetraoxo-7-methyl-17 Alpha ,21-dihydroxy-A-nor-B-homo-pregnene.
 8. Delta 1-3,6,20-Trioxo-11 Beta ,17 Alpha ,21-trihydroxy-A-nor-B-homo-pregnene. 